Converging dopamine pathways onto basolateral amygdala neurons encode exploration decisions

  • Neuron. 2026 Mar 18;114(6):1131-1151.e6. doi: 10.1016/j.neuron.2025.12.007.
Chaowen Zheng  1 ,  Xiaoying Liu  1 ,  Anqi Wei  2 ,  Bing Liu  3 ,  Qianyun Zhang  2 ,  Junjie Jiang  2 ,  Xiaofeng Gao  2 ,  Hong Fan  2 ,  Anran Zhao  2 ,  Xueting Duan  2 ,  Xu Cheng  4 ,  Haiyao Liu  2 ,  Niki Gooya  5 ,  Fenghan Mao  2 ,  Aomei An  2 ,  Shuaijie Zhong  2 ,  Jie Jian  4 ,  Wenxin Shen  4 ,  Xingyao Dong  4 ,  Kaikai Yang  4 ,  Bianbian Wang  2 ,  Ziyang Li  2 ,  Jingxiao Huo  2 ,  Jingyu Yao  2 ,  Weiwei Li  6 ,  Yu Lu  2 ,  Junxi Kang  7 ,  Kai Huang  2 ,  Nan Dong  2 ,  Yang Chen  2 ,  Qian Song  2 ,  Zigang Huang  2 ,  Rong Huang  2 ,  Zhenli Xie  2 ,  Yan Li  8 ,  Shuqin Zhan  2 ,  Han Xu  9 ,  Yong Jiang  4 ,  Chunxiang Zhang  4 ,  Dan Xu  2 ,  Haowen Liu  10 ,  Jinghong Ma  11 ,  Yuqing Zhang  12 ,  Huadong Xu  13 ,  Xinjiang Kang  14 ,  Changhe Wang  15
Affiliations
  • 1. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
  • 2. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
  • 3. LFC Laboratory and Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing 400064, China.
  • 4. Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
  • 5. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 6. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Department of Acupuncture, Massage, and Rehabilitation, Shaanxi Provincial Hospital of Chinese Medicine, Xi'an 710003, China.
  • 7. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; School of Physical Education, Taishan University, Tai'an 271000, China.
  • 8. The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710049, China.
  • 9. Department of Neurobiology and Department of Psychiatry of the Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 10. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: [email protected].
  • 11. Department of Neurology and Department of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Electronic address: [email protected].
  • 12. Department of Neurology and Department of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Electronic address: [email protected].
  • 13. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China. Electronic address: [email protected].
  • 14. Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China; College of Life Sciences, Liaocheng University, Liaocheng 252059, China. Electronic address: [email protected].
  • 15. Neuroscience Research Center, National Key Laboratory for High Energy Pulsed Power, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China; Department of Neurology, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China. Electronic address: [email protected].
PMID: 41638204 DOI: 10.1016/j.neuron.2025.12.007
Abstract

Exploration is a fundamental innate behavior essential for securing survival-necessary resources, but it also increases risks. However, the neural mechanisms encoding exploration decisions remain unknown. Here, we show that social companionship motivates both innate-driven and experience-dependent explorations in mice. Dopaminergic neurons in the ventral tegmental area (VTADA neurons) determine exploration decisions by encoding risky vigilance (via phasic firing) and exploration motivation (via tonic firing). Two subpopulations of VTADA neurons co-innervate the same population of basolateral amygdala neurons via direct and indirect pathways. Tonic firing-biased DA-D2R transmission in the medial prefrontal cortex (indirect pathway) mediates exploratory behaviors, which are reinforced by social interactions, while phasic firing-biased DA-D1R transmission in the direct pathway mediates avoidant behaviors. The dynamic balance between these two competing DA pathways coordinately encodes exploration decisions. These findings establish the VTADA neuron as a central hub and the circuit integration of biased DA transmission as a central mechanism encoding exploration decisions.

Keywords
D1R; D2R; dopaminergic neurons; exploration; firing pattern; social interaction; ventral tegmental area.
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